A nanoscale study of particle friction in a pharmaceutical system.

Studies of single particle interactions in dry powder inhaler (DPI) formulations using atomic force microscopy (AFM) have recently grown in popularity. Currently, these experiments are all based on measuring particle adhesion forces. We broaden this approach by presenting a novel AFM friction study of single particles in a pharmaceutical system, to examine forces acting parallel to a surface. The sliding friction signal of lactose particles attached to AFM cantilevers was recorded in lateral force (LF) mode over 5 microm x 5 microm areas on five different surfaces chosen to represent both relevant inter-particle and particle-surface interactions. A ranking of friction forces was obtained as follows: glass approximately equal to zanamivir >zanamivir-magnesium stearate (99.5%/0.5%, w/w) blend approximately equal to magnesium stearate approximately equal to PTFE. The addition of magnesium stearate to the zanamivir surface dominated and significantly reduced the friction (Kruskal-Wallis test, P<0.001). AFM images of the contacting asperities of the lactose particles show changes in contact morphology due to two processes. Firstly the asperity wears flat due to abrasion and secondly small magnesium stearate particles transfer onto the asperity. It is proposed that in combination with AFM particle adhesion measurements, this method could be used to screen new formulations and the effectiveness of tertiary components in modifying carrier-drug interactions.